Erratum: Inflammatory extracellular vesicles prompt heart dysfunction via TLR4-dependent NF-κB activation: Erratum.

[This corrects the article DOI: 10.7150/thno.39072.

Inflammatory extracellular vesicles prompt heart dysfunction via TRL4-dependent NF-κB activation.

: After myocardial infarction, necrotic cardiomyocytes release damage-associated proteins that stimulate innate immune pathways and macrophage tissue infiltration, which drives inflammation and myocardial remodeling. Circulating inflammatory extracellular vesicles play a crucial role in the acute and chronic phases of ischemia, in terms of inflammatory progression. In this study, we hypothesize that the paracrine effect mediated by these vesicles induces direct cytotoxicity in cardiomyocytes.

Exosomal Expression of CXCR4 Targets Cardioprotective Vesicles to Myocardial Infarction and Improves Outcome after Systemic Administration.

Cell therapy has been evaluated to enhance heart function after injury. Delivered cells mostly act via paracrine mechanisms, including secreted growth factors, cytokines, and vesicles, such as exosomes (Exo). Intramyocardial injection of cardiac-resident progenitor cells (CPC)-derived Exo reduced scarring and improved cardiac function after myocardial infarction in rats.

ALDH1A3 Is the Key Isoform That Contributes to Aldehyde Dehydrogenase Activity and Affects Proliferation in Cardiac Atrial Appendage Progenitor Cells.

High aldehyde dehydrogenase (ALDH) activity has been reported in normal and cancer stem cells. We and others have shown previously that human ALDH cardiac atrial appendage cells are enriched with stem/progenitor cells. The role of ALDH in these cells is poorly understood but it may come down to the specific ALDH isoform(s) expressed.

Cardioprotection by cardiac progenitor cell-secreted exosomes: role of pregnancy-associated plasma protein-A.

Aims: Cell therapy trials using cardiac-resident progenitor cells (CPCs) and bone marrow-derived mesenchymal stem/progenitor cells (BMCs) in patients after myocardial infarction have provided encouraging results. Exosomes, nanosized extracellular vesicles of endosomal origin, figure prominently in the bioactivities of these cells. However, a head-to-head comparison of exosomes from the two cell types has not been performed yet.

Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade.

Aim: Human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are likely to revolutionize electrophysiological approaches to arrhythmias. Recent evidence suggests the somatic cell origin of hiPSCs may influence their differentiation potential. Owing to their cardiomyogenic potential, cardiac-stromal progenitor cells (CPCs) are an interesting cellular source for generation of hiPSC-derived cardiomyocytes.

Exosomes for Intramyocardial Intercellular Communication.

Cross-talk between different cell types plays central roles both in cardiac homeostasis and in adaptive responses of the heart to stress. Cardiomyocytes (CMs) send biological messages to the other cell types present in the heart including endothelial cells (ECs) and fibroblasts. In turn, CMs receive messages from these cells.

Conditioned medium from human amniotic mesenchymal stromal cells limits infarct size and enhances angiogenesis.

The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators.

Combination of miRNA499 and miRNA133 exerts a synergic effect on cardiac differentiation.

Several studies have demonstrated that miRNA are involved in cardiac development, stem cell maintenance, and differentiation. In particular, it has been shown that miRNA133, miRNA1, and miRNA499 are involved in progenitor cell differentiation into cardiomyocytes. However, it is unknown whether different miRNA may act synergistically to improve cardiac differentiation.

Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction.

Aims: Recent evidence suggests that cardiac progenitor cells (CPCs) may improve cardiac function after injury. The underlying mechanisms are indirect, but their mediators remain unidentified. Exosomes and other secreted membrane vesicles, hereafter collectively referred to as extracellular vesicles (EVs), act as paracrine signalling mediators.

Allogeneic lethally irradiated cord blood mononuclear cells in no-option critical limb ischemia: a "box of rain".

Critical limb ischemia (CLI) is burdened by a 40% major amputation rate, and a 5-year life expectancy <50%. We report the first in-human injection of lethally γ-irradiated non-human leukocyte antigen (HLA)-matched cord blood (CB)-derived mononuclear cells in a no-option CLI patient, to induce therapeutic neo-angiogenesis, with evidence of successful outcome supported by clinical findings (ulcer healing and pain relief), instrumental assessment (transcutaneous O2 pressure, ankle/brachial index, and contrast-enhanced ultrasonography), and histological demonstration of muscular tissue repair and capillary network expansion. If our approach will be confirmed, the huge number of CB units currently discarded might be redirected toward regenerative medicine purposes, leading to cutting-edge solutions for important unmet clinical needs, such as ischemic diseases, which remain the main cause of disability and mortality in western countries.

Mesenchymal stem cell therapy for heart disease.

Mesenchymal stem cells (MSC) are adult stem cells with capacity for self-renewal and multi-lineage differentiation. Initially described in the bone marrow, MSC are also present in other organs and tissues. From a therapeutic perspective, because of their easy preparation and immunologic privilege, MSC are emerging as an extremely promising therapeutic agent for tissue regeneration and repair.

Sera of patients with celiac disease and neurologic disorders evoke a mitochondrial-dependent apoptosis in vitro.

Background & Aims: The mechanisms underlying neurologic impairment in celiac disease remain unknown. We tested whether antineuronal antibody-positive sera of patients with celiac disease evoke neurodegeneration via apoptosis in vitro.

Methods: SH-Sy5Y cells were exposed to crude sera, isolated immunoglobulin (Ig) G and IgG-depleted sera of patients with and without celiac disease with and without neurologic disorders, and antineuronal antibodies.

[Recent insights into the pathogenesis of abdominal symptoms in functional bowel disorders].

In the gut, 5-HT acts as a paracrine signalling molecule released by enterochromaffin cells and as a transmitter released by some descending serotonergic interneurons. It has a prominent role in the regulation of motility, vascular tone, secretion and perception both in normal and under certain pathophysiological conditions, such as the carcinoid syndrome and the irritable bowel syndrome (IBS). Serotonin is known to markedly influence bowel function by activating at least five receptor types (5-HT(1,2,3,4,7)).

5-HT7 receptors modulate peristalsis and accommodation in the guinea pig ileum.

Background & Aims: The 5-hydroxytryptamine 7 (5-HT7) receptors mediate intestinal smooth muscle relaxation. In this study, we evaluated the expression of 5-HT7 receptors in the guinea pig ileum and their role in peristalsis and accommodation of the circular muscle.

Methods: We used immunohistochemistry and confocal microscopy with whole tissue and cultured myenteric neurons.